Current work in our laboratory is focused on two projects: (a) We are tryping to understand the role of aminoacylation of tRNA in the regulation of protein degradation in mammalian cells. We have obtained strong evidence of the association between these two processes from studies of histidine starvation in Chinese Hamster Ovary cells with mutations in histidyl tRNA synthetase, as well as the effects of histidinol, a competitive inhibitor of this enzyme. (b) We are also interested in the pathways of breakdown of cellular proteins. We are taking advantage of our discovery that bestatin, a competitive inhibitor of aminopeptidases, permits the accumulation of small peptide intermediates in the degradation of analog-containing globin by intact mouse reticulocytes and soluble cell-free systems derived from them. We have provided evidence that the soluble system represents the process as its occurs in vivo.